4-diphenyl (methyl/hydroxymethyl) spiropiperidines and process



3,019,228 Patented J an. 30, 1962 This invention relates to 4-diphenylmethylspiropiperidines optionally a-hydroxylated, and a process for the manufacture thereof. More particularly, this invention relates to spiropiperidines of the formula wherein R represents hydrogen or a hydroxy radical, X represents halogen, and n represents either 1 or 2. Among the halogens represented by X, especially chlorine, bromine, and iodine are preferred. Those skilled in the art will appreciate that when n in the formula is 1, the contemplated compounds are spiro [piperidine-l,1'-pyrrolidinium] halides, whereas when n is 2, the compounds contemplated are l,l-spirobipiperidinium halides.

The compounds to which this invention relates are useful because of their valuable pharmacological properties. Thus, for example, they exert a depressant efiect on the central nervous system and, accordingly, are anti-emetic and barbiturate-potentiating agents. Further, they manifest anti-secretory and anti-fungal activity.

Manufacture of the subject compositions proceeds by heating an appropriate diphenyhnethylpiperidine with a dihaloalkane of the formula X-CH CH CH (CH ),,-X

(R, X, and n being defined as before) in an inert solvent such as chloroform, acetone, butanone, methanol, butanol, etc. Temperatures of the order of 60-100 for periods of time ranging from 1 to 48 hours are efficacious, and an alkaline catalyst such as sodium or potassium carbonate is commonly present.

The following examples describe in detail certain of the compounds illustrative of the present invention and methods which have been devised for their manufacture. However, the invention is not to be construed as limited thereby, either in spirit or in scope, since it will be apparent to those skilled in the art that many modifications, both of materials and of methods, may be practiced without departing from the purpose and intent of this disclosure. In the examples hereinafter detailed, temperatures are given in degrees centigrade and relative amounts of materials in parts by weight, except as otherwise noted.

2 EXAMPLE 1 4-diphenylhydroxymelhylspiro[piperidine-1,1 pyrrolidinium] bromide A mixture of 53 parts of.a,a-diphenyl-4-pipe1idinemethanol, 47 parts of 1,4-dibromobutane, and 28 parts of finely powdered anhydrous potassium carbonate in 1250 parts of l-butanol is heated at the boiling point under rellux with vigorous agitation for 19 hours. Insoluble solids are removed from the hot reaction mixture by filtration and exhaustively extracted with hot l-butanol.

rom the resultant extracts and from the reaction mixture filtrate, on chilling, there precipitate iridescent needles of pure 4-diphenylhydroxymethylspiro[piperidine 1,1- pyrrolidinium] bromide which, recovered by filtration and dried in air, melts at approximately 3103l1 with decomposition and gas evolution. The product has the formula EXAMPLE 2 4-diphenylhydroxymethyl-I ,1 '-spir0bipiperidinium bromide EXAMPLE 3 4-diplzenylmethylspiro[piperidine-1,1 '-pyrr0lidinium] bromide Using essentially the technique of the preceding Example 2, but substituting 50 parts of 4-(diphenylmethyl) piperidine and 47 parts of 1,4-dibromobutane for the a,adiphenyl-4-piperidinemethanol and 1,5-dibromopentane called for therein, respectively, one obtains massive colorless needles of 4-diphenylmethylspiro[piperidine-1,l'-pyrrolidinium} bromide, melting at 279-281. The product has'the formula @WQ Ll dinium bromide which, recrystallized from l-butanol, 20

melts at approximately 323324 with gas evolution. The product has the formula What is claimed is: 1. A compound of the formula 4 wherein R is selected from the group consisting of hydrogen and hydroxy radicals and n is a positiveinteger amounting to less than 3.

2. A compound of the formula wherein n is a positive integer amounting to less than 3.

3. 4 diphenylhydroxymethylspiro[piperidine 1,1- py'rrolidinium] bromide.

4. 4 diphenylhydroxymethyl 1,1 spirobipiperidinium bromide.

5. A compound of the formula wherein n is a positive integer amounting to less than 3.

6. 4-diphenylmethylspiro[piperidine 1,1 pyrrolidinium] bromide.

7 4.-diphenylmethyl.- 1,1 spirobiperidinium bromide.

References Cited in the file of this patent 40 UNITED STATES PATENTS 2,486,792 Miescher et al. Nov. 1, 1949 2,486,793 Miescher et al. Nov. 1, 1949 2,486,794 Miescher et al. Nov. 1, 1949 45 2,748,143 Erickson May 29, 1956 

1. A COMPOUND OF THE FORMULA 